WO2011107932A1 - Dispositif d'administration de médicament - Google Patents

Dispositif d'administration de médicament Download PDF

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Publication number
WO2011107932A1
WO2011107932A1 PCT/IB2011/050860 IB2011050860W WO2011107932A1 WO 2011107932 A1 WO2011107932 A1 WO 2011107932A1 IB 2011050860 W IB2011050860 W IB 2011050860W WO 2011107932 A1 WO2011107932 A1 WO 2011107932A1
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WO
WIPO (PCT)
Prior art keywords
drug delivery
delivery device
drug
anchoring element
reservoir
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/IB2011/050860
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English (en)
Inventor
Michael Ariel Vardi
Alon Shalev
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
ESTIMME Ltd
Original Assignee
ESTIMME Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by ESTIMME Ltd filed Critical ESTIMME Ltd
Publication of WO2011107932A1 publication Critical patent/WO2011107932A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M31/00—Devices for introducing or retaining media, e.g. remedies, in cavities of the body

Definitions

  • the present invention relates to the field of drug delivery, and more particularly, to an implantable drug delivery device.
  • Intratympanic delivery involves depositing the therapeutic agent in the middle ear, relying primarily on diffusion through the round window membrane (RWM) for access to the scala tympani.
  • Intratympanic delivery must rely solely on diffusion through the round window and for dispersion throughout the scala tympani. Therefore, access to the apical regions of the scala tympani can be limited, and large concentration gradients may develop.
  • the RWM presents a physical barrier to delivery. A great deal of variability of condition and thickness of the membrane across population has been observed, limiting dosage control from patient to patient.
  • cavities in the body are usually open, and present a challenge to maintain an appropriate concentration of the drug in proximity to the application area, e.g. the RWM.
  • drug may be drained into other regions in the middle ear and be removed altogether through the Eustachian tube.
  • Passive drug delivery systems are designed to deliver drug compounds with specific kinetic profiles using local triggers for release, such as hydrolysis in the in vivo environment, or in response to local stimuli such as temperature or pH.
  • Drug may be dispersed within a matrix or contained within a reservoir encapsulated by a shell of bulk polymer, depending upon the specific application.
  • Anatomical variations can significantly alter the pathway from the delivery site to the round window. These include extraneous or false membranes, fibrous tissue and fatty plugs, and may be present in as high as one third of all patients.
  • Additional approaches are: (i) Round Window Microcatheters ( ⁇ -CathTM and e- CathTM) developed by IntraEAR and later acquired by Durect in 1999, currently used for local drug delivery to the middle or inner ear for tinnitus by Neurosystec, (ii) Silverstein Micro WickTM for treatment of Meniere's related vertigo by perfusion of gentamicin, (iii) an implantable Alzet osmotic pump provides the means for continuous sustained delivery in a very small volume with simple form factor, (iv) various intracochlear drug delivery methods and cochlear prosthesis-based delivery.
  • ⁇ -CathTM and e- CathTM Round Window Microcatheters developed by IntraEAR and later acquired by Durect in 1999, currently used for local drug delivery to the middle or inner ear for tinnitus by Neurosystec
  • Silverstein Micro WickTM for treatment of Meniere's related vertigo by perfusion of gentamicin
  • WIPO Publication No. 2010143181 which is incorporated herein by reference in its entirety, discloses an electrode, and a minimally-invasive auditory implant system employing the electrode, for treating hearing disorders by electrically stimulating tissues in the middle ear.
  • the electrode employs a structure which switches between narrow and spread shapes, facilitating the electrode insertion into the site, securing the electrode against vibration or permanent movement, and optimizing the current density.
  • Embodiments of the present invention provide a drug delivery device comprising: a drug reservoir coupled with a delivery element arranged to deliver the drug from the reservoir to a specified location; and an anchoring element arranged to anchor and support the drug reservoir in a vicinity of the specified location and the delivery element at the specified location, wherein the anchoring element is attachable to a cavity and has at least two states: a collapsed state arranged to enable insertion of the anchoring element into the cavity in a minimally invasive procedure; and an operative state arranged to affix the anchoring element to the cavity, wherein the anchoring element is arranged to change from the collapsed state to the operative state upon fulfillment of a specified condition.
  • Figure 1 is a schematic illustration of a drug delivery device positioned in the middle ear, according to some embodiments of the invention.
  • Figures 2A and 2B are schematic illustrations of an anchoring element of the drug delivery device in collapsed an operative states, according to some embodiments of the invention
  • Figures 3A and 3B are schematic illustrations of the drug delivery device in collapsed an operative states, according to some embodiments of the invention.
  • FIGS. 4A to 4C are schematic illustrations of toroidal drug delivery devices, according to some embodiments of the invention.
  • Figures 5A and 5B are schematic illustrations of the drug delivery device with hooked protrusions in the anchoring element, in collapsed an operative states, according to some embodiments of the invention
  • Figures 6 and 7 are schematic illustrations of toroidal drug delivery devices in the paranasal sinuses, according to some embodiments of the invention
  • Figure 8 is a schematic illustration of the drug delivery device with hooked protrusions in the anchoring element, in the operative state in the hypotympanum, according to some embodiments of the invention.
  • FIGS 9 and 10 are schematic illustrations of filling methods of the drug delivery device, according to some embodiments of the invention.
  • Figures 11A-11D are schematic illustrations of an ellipsoidal drug delivery device in collapsed and operative states and in the paranasal sinuses, according to some embodiments of the invention.
  • Figure 12 is a high level schematic block diagram illustrating components of the drug delivery device, according to some embodiments of the invention.
  • Figure 13 is a high level schematic flowchart illustrating a method of delivering a drug to a specified location, according to some embodiments of the invention.
  • Figure 1 is a schematic illustration of a drug delivery device 100 positioned in the middle ear, according to some embodiments of the invention
  • Figures 2A and 2B are schematic illustrations of an anchoring element 130 of drug delivery device 100 in collapsed an operative states (101 and 102, respectively), according to some embodiments of the invention
  • Figures 3A and 3B are schematic illustrations of drug delivery device 100 in collapsed an operative states (101 and 102, respectively), according to some embodiments of the invention.
  • Drug delivery device 100 comprises a drug reservoir 110 (e.g. compressible, elastic and water-tight) coupled with a delivery element 120 arranged to deliver the drug from reservoir 110 to a specified location 99.
  • Drug reservoir 110 may be elastic (e.g. have an outer elastic chassis) to the extent that drug is excreted under pressure from drug reservoir 110 through delivery element 120.
  • Drug delivery device 100 may further comprise a control unit 140 arranged to control delivery element 120, and an anchoring element 130.
  • Anchoring element 130 is attachable to a cavity 90 and has at least two states: a collapsed state 131 arranged to enable insertion of anchoring element 130 into cavity 90 in a minimally invasive procedure; and an operative state 132 arranged to affix anchoring element 130 to cavity 90.
  • Cavity 90 may comprise a bone cavity with epithelial tissue, a cartilage cavity or any other cavity which is stiff enough to support and allow anchoring of anchoring element 130
  • Anchoring element 130 is arranged to change (e.g. self- expand) from collapsed state 131 to operative state 132 upon fulfillment of a specified condition.
  • Anchoring element 130 may have a form that attaches to cavity 90 upon expansion to the operative state.
  • Anchoring element 130 is arranged to anchor and support drug reservoir 110 in a vicinity of specified location 99 and to anchor and support delivery element 120 at specified location 99.
  • Specified location 99 may be within a second cavity 95.
  • Second cavity 95 may be the same cavity as cavity 90 or an adjacent cavity.
  • Second cavity 95 may be a bone cavity with epithelial tissue, a cartilage cavity or any other cavity to which drug may be delivered.
  • FIG. 1 and 8-10 illustrates drug delivery device 100 in the inner ear (comprising malleus 71, incus 72, stapes 73 at oval window, vestibular organ 74, cochlea 75 and its basis 76), e.g. arranged to deliver the drug to the round window as specified location 99.
  • anchoring element 130 may be arranged to be attachable to Eustachian tube 92 or hypotympanum 94.
  • anchoring element 130 may be cylindrical, or comprise a cylindrical network (or mesh) that attaches to the circumference of an orifice or a lumen of Eustachian tube 92.
  • anchoring element 130 may have a form that attaches to hypotympanum 94 upon expansion to the operative state, such as a conical form comprising a membrane 129 spun by bracings 128 interconnected at a common basis 127 ( Figures 2A, 2B).
  • Drug delivery device 100 may be part of a drug delivery system (not shown) comprising additionally an applicator 149 (illustrated schematically in Figure 12) arranged to introduce (releasably deploying) drug delivery device 100 to a vicinity of specified location 99 (e.g. within hypotympanum 94) and deliver anchoring element 130 in collapsed state 131 to cavity 90.
  • an applicator 149 illustrated schematically in Figure 12
  • specified location 99 e.g. within hypotympanum 94
  • Applicator 149 may be further arranged to deliver anchoring element 130 in collapsed state 131 to cavity 90 and transfer anchoring element 130 to operative state 132 upon releasing anchoring element 130 from applicator 149. Applicator 149 may actuate the transition anchoring element 130 from collapsed 131 to operative state 132.
  • Applicator 149 may be any standard endoscopic equipment, for example, a balloon arranged to facilitate a transition of anchoring element 130 from collapsed state 131 to operative state 132. Applicator 149 may further comprise an endoscopic visualization channel.
  • Either drug reservoir 110 in its operative state 111 or delivery element 120 is arranged to fit into the hypotympanum.
  • Figures 4A to 4C are schematic illustrations of toroidal drug delivery devices 100, according to some embodiments of the invention.
  • Figures 6 and 7 are schematic illustrations of toroidal drug delivery devices 100 in paranasal sinuses 96, according to some embodiments of the invention.
  • Drug reservoir 110 may be ellipsoidal.
  • drug reservoir 110 may be toroidal ( Figures 4A, 4B, 4C) to allow fluid communication through an axial hollow 126 in the toroid.
  • Anchoring element 130 may be integrated in the toroidal drug reservoir 110 (e.g. Figure 4C).
  • Toroidal drug reservoir 110 may be positioned within a fluid conducting cavity, such as Eustachian tube 92 or sinuses 96. The dimensions and sizes of drug reservoir 110 may be adapted to the intended position thereof.
  • Toroidal drug reservoir 110 may have integrated anchoring element 130, or anchoring element 130 may support drug reservoir 110 internally, at hollow 126.
  • anchoring element 130 may position drug reservoir 110 to keep Eustachian tube 92 in fluid communication with the inner ear through hollow 126 and in place in respect to specified location 99.
  • Drug reservoir 110 may be formed to fit into hypotympanum 94, or sinus 96 and comprise a conduit 122 arranged to deliver the drug from drug reservoir 110 to specified location 99.
  • Anchoring element 130 may comprise supporting elements 121 arranged to support conduit 122. Supporting elements 121 may be connected to an extension 128A of anchoring element 130 (e.g. of bracing 128).
  • Conduit 12 may comprise a stricture (not shown) that is arranged to limit a rate of delivery of the drug therethrough to specified location 99. The width of the stricture may be controlled by control unit 140 or externally.
  • Figures 5A and 5B are schematic illustrations of drug delivery device 100 with hooked protrusions 133 in anchoring element 130, in collapsed and operative states (101, 131 and 102, 132 respectively), according to some embodiments of the invention.
  • Figure 8 is a schematic illustration of drug delivery device 100 with hooked protrusions 133 in anchoring element 130, in operative state 102 in hypotympanum 94, according to some embodiments of the invention.
  • Anchoring element 130 may comprise a plurality of elongated protrusions 133 fixated at one end 133 A and arranged to spread apart at their free ends 133B in operative state 132. Free ends 133B of protrusions 133 may be hooked to enhance attachment of anchoring element to cavity 90 (such as hypotympanum 94).
  • anchoring element 130 may comprise a plurality of flexible ellipses 134 interconnected at two common apices 134A to define a spheroid, that is prolate in collapsed state 131 ( Figure 11 A) and oblate in operative state 132 ( Figure 11B).
  • Figures 7A, 7B illustrate drug delivery device 100 within sinuses 96.
  • Anchoring element 130 may be made of a shape memory alloy that is pre-formed to an operative state shape.
  • Anchoring element 130 may be made of a super elastic metal, such as nitinol or elginoy. Anchoring element 130 may then be inserted in collapsed state 131 and expand to the pre-formed shape upon the specified condition, for example body warmth or reaching a specified body temperature.
  • Anchoring element 130 in operative state 132 may be arranged to receive, support and fixate drug reservoir 110.
  • Delivery element 120 may comprise a tip 123 arranged to deliver the drug to specified location 99.
  • Tip 123 may be porous or spongeous, to optimize drug delivery.
  • Delivery element 120 may be arranged to fit into round window niche 95, and may comprise a sealing element 124 in proximity to tip 123 ( Figures 4A, 4B, 8, 11A, 11B) arranged to seal round window niche 95 to prevent leakage of the drug out of round window niche 95.
  • Sealing element 124 may comprise one or more silicon discs ( Figure 8), and may be structurally integrated in tip 123A ( Figure 4C).
  • Drug delivery device 100 may further comprise an electroporation unit 123B ( Figures 11A, 11B) comprising one or more electrodes 123C, arranged to enhance a permeability of a membrane at specified location 99, for example of the round window. Electroporation unit 123B may be integrated with tip 123 form a functional tip 123D for delivering the drug.
  • Electroporation unit 123B may be integrated with tip 123 form a functional tip 123D for delivering the drug.
  • the drug itself may be is selected from any anti inflammatory drugs, N-Methyl- D-aspartate (NMDA) antagonists, anti-oxidant drugs, nerve growth factors, cyto-toxic drugs, and cyto-static drugs.
  • the drug may be selected to treat an ear disease, such as Tinnitus, Meniere's disease, Sudden hearing loss, etc.
  • the drug may be selected to facilitate ion current, and drug delivery device 100 may further comprise a stimulation electrode (not shown) in galvanic contact with the drug.
  • Figures 9 and 10 are schematic illustrations of filling methods of drug delivery device 100, according to some embodiments of the invention.
  • Drug reservoir 110 may be fillable through ear drum 93 ( Figure 9), or through any other soft tissue near the location of drug reservoir 110 by filling device 150.
  • drug reservoir 110 may be fillable endoscopically, e.g. through Eustachian tube 92 ( Figure 10) or through sinuses 96 or the nasal cavity.
  • Filling device 150 may comprise a syringe ( Figure 9), e.g. with a needle, or a drug-loading/refilling catheter ( Figure 10).
  • Anchoring element 130 may comprise a proximal barrel shaped mesh having extension 128 supporting delivery element 120 (e.g. conduit 122) and extension 128B arranged to support drug reservoir 110 in place.
  • Drug delivery device 100 may comprise retrieval elements (not shown) connected e.g. to anchoring element 130 of drug reservoir 110 and arranged to allow endoluminal retrieval of drug delivery device 100 as a whole, or drug reservoir 110 on itself, e.g. by an endoscopic intervention.
  • the retrieval elements may transfer anchoring element 130 from operative state 132 back to collapsed state 131 before retrieval.
  • the retrieval elements may comprise retrieval handles arranged to engage a retrieval apparatus provided with means of transitioning anchoring element 130 from operative state 132 back to collapsed state 131 and its subsequent disposition into a generally elongated sheath.
  • Figure 12 is a high level schematic block diagram illustrating components of drug delivery device 100, according to some embodiments of the invention.
  • Control unit 140 may comprise an internal power source 141, or may be arranged to inductively receive power by an inductive element 142 (an implantable energy conversion unit), e.g. by an attached coil 145, from an external (extra-corporeal) power source 141A.
  • an inductive element 142 an implantable energy conversion unit
  • Control unit 140 may comprise an internal power source 141, or may be arranged to inductively receive power by an inductive element 142 (an implantable energy conversion unit), e.g. by an attached coil 145, from an external (extra-corporeal) power source 141A.
  • Control unit 140 may be internal or external (140A), or device 100 may comprise both internal control unit 140 and external control unit 140A.
  • inductive element may be connected to reservoir 110 and inductive power supply therethrough may actuate drug delivery.
  • External power may be delivered to drug delivery device 100 in mechanical, electromagnetic or magnetic forms.
  • Control unit 140 may comprise a controller (e.g. an electronic processor embedded in PCB) arranged to manage drug delivery and power use of device 100.
  • Control unit 140 may further comprise a pump (not shown) arranged to deliver the drug through delivery element 120.
  • FIG. 13 is a high level schematic flowchart illustrating a method 200 of delivering a drug to a specified location, according to some embodiments of the invention.
  • Method 200 comprises the following stages: inserting the drug in a reservoir connected to an anchoring element in a collapsed state to a vicinity of the specified location (stage 205); attaching the anchoring element in a cavity in the vicinity of the specified location (stage 210), by transforming the anchoring element from the collapsed to an operative state (stage 215); and releasing the drug from the reservoir (stage 220).
  • Method 200 may further comprise pre-forming the anchoring element in the operative state (stage 214), for example from a super-elastic metal such as nitinol, or elginoy.
  • Method 200 may further comprise controlling the drug release 220 from the reservoir (stage 222), externally (e.g. by a mechanical of electromagnetic signal, or internally, e.g. by reshaping of the reservoir upon a specified conditions, such as a body temperature).
  • Method 200 may further comprise sealing a second cavity that surrounds the specified location (224), to prevent drug leakage and allow a better control of the delivered amount of drug and the delivery location, and furthermore allow using smaller amounts of drug.
  • Method 200 may further comprise re-filling the reservoir without removing the anchoring element from the cavity (stage 226), for example endoscopically or through neighboring soft tissue, such as the ear drum in case of drug delivery to the inner ear, or nose cartilage in case of drug delivery to the paranasal sinuses.
  • Method 200 may further comprise integrating the anchoring element in the reservoir (stage 228), for example when the reservoir is toroidal with the anchoring element as its external layer.

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  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Anesthesiology (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Hematology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Infusion, Injection, And Reservoir Apparatuses (AREA)

Abstract

Cette invention concerne un dispositif d'administration de médicament comprenant un réservoir de médicament couplé avec un élément d'administration conçu pour délivrer le médicament depuis le réservoir jusqu'à un site spécifique ; et un élément d'ancrage conçu pour ancrer et supporter le réservoir de médicament à proximité du site spécifique et l'élément d'administration au site spécifique. L'élément d'ancrage peut être fixé à une cavité et possède un état écrasé conçu pour permettre l'insertion de l'élément d'ancrage dans la cavité lors d'une procédure très peu invasive ; et un état fonctionnel conçu pour fixer l'élément d'ancrage à la cavité. L'élément d'ancrage est conçu pour passer de l'état écrasé à l'état fonctionnel une fois une condition spécifique remplie.
PCT/IB2011/050860 2010-03-01 2011-03-01 Dispositif d'administration de médicament Ceased WO2011107932A1 (fr)

Applications Claiming Priority (2)

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US30899810P 2010-03-01 2010-03-01
US61/308,998 2010-03-01

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WO2011107932A1 true WO2011107932A1 (fr) 2011-09-09

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2020115674A1 (fr) * 2018-12-05 2020-06-11 Cochlear Limited Stockage et administration de substance thérapeutique

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6685697B1 (en) * 1998-12-04 2004-02-03 Durect Corporation Controlled release system for delivering therapeutic agents into the inner ear
US20050043680A1 (en) * 2001-11-29 2005-02-24 Jerome Segal Mechanical apparatus and method for dilating and delivering a therapeutic agent to a site of treatment
US20080009836A1 (en) * 2004-01-29 2008-01-10 Jason Fiering Drug delivery apparatus
US20080154250A1 (en) * 2004-04-21 2008-06-26 Acclarent, Inc. Devices, Systems and Methods For Diagnosing and Treating Sinusitis and Other Disorders of the Ears, Nose and/or Throat
US20080319424A1 (en) * 2004-04-21 2008-12-25 Acclarent, Inc. Devices and Methods for Delivering Therapeutic Substances for the Treatment of Sinusitis and Other Disorders
US20090253914A1 (en) * 2004-12-14 2009-10-08 Merck Patent Gmbh Process for the preparation of onium salts with dialkylphosphate, dialkylphosphinate or (o-alkyl)alkyl- or alkylphosphonate anions having a low halide content

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6685697B1 (en) * 1998-12-04 2004-02-03 Durect Corporation Controlled release system for delivering therapeutic agents into the inner ear
US20050043680A1 (en) * 2001-11-29 2005-02-24 Jerome Segal Mechanical apparatus and method for dilating and delivering a therapeutic agent to a site of treatment
US20080009836A1 (en) * 2004-01-29 2008-01-10 Jason Fiering Drug delivery apparatus
US20080154250A1 (en) * 2004-04-21 2008-06-26 Acclarent, Inc. Devices, Systems and Methods For Diagnosing and Treating Sinusitis and Other Disorders of the Ears, Nose and/or Throat
US20080319424A1 (en) * 2004-04-21 2008-12-25 Acclarent, Inc. Devices and Methods for Delivering Therapeutic Substances for the Treatment of Sinusitis and Other Disorders
US20090253914A1 (en) * 2004-12-14 2009-10-08 Merck Patent Gmbh Process for the preparation of onium salts with dialkylphosphate, dialkylphosphinate or (o-alkyl)alkyl- or alkylphosphonate anions having a low halide content

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2020115674A1 (fr) * 2018-12-05 2020-06-11 Cochlear Limited Stockage et administration de substance thérapeutique

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